Intra-arterial anti-oxidant power negatively correlates with white matter injury, and oxidative stress positively correlates with disability in daily activities

2021 ◽  
Vol 336 ◽  
pp. 113539
Author(s):  
Norihito Shimamura ◽  
Takeshi Katagai ◽  
Nozomi Fujiwara ◽  
Kouta Ueno ◽  
Ryouta Watanabe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
White Matter ◽  
White Matter Injury ◽  
Daily Activities ◽  
Anti Oxidant ◽  
And Oxidative Stress

scholarly journals Short-term Diesel Exhaust Exposure Results in Neuroinflammation and White Matter Injury

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 640-640
Author(s):  
Krista Lamorie-Foote ◽  
Kristina Shkirkova ◽  
Qinghai Liu ◽  
Constantinos Sioutas ◽  
Todd Morgan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
White Matter ◽  
Corpus Callosum ◽  
Diesel Exhaust ◽  
Time Course ◽  
Ambient Air ◽  
White Matter Injury ◽  
Ambient Air Pollution ◽  
Diesel Exhaust Particulate ◽  
And Oxidative Stress

Abstract Ambient air pollution (AAP) exposure is associated with white matter injury and cognitive decline in older adults(Chen et al. 2020,Erickson et al. 2020). Neuroinflammation and oxidative stress may contribute to this white matter injury. Diesel exhaust particulate matter (DEP) is a neurotoxic component of AAP.This study characterizes the time course by which neuroinflammation/oxidative stress occurs and results in white matter injury following DE exposure in a murine model. DEP (Sigma) was re-aerosolized for exposure. Mice were exposed to 100 µg/m3 DEP or filtered air (FA) for 5 hours (n=8/group), 100 hours (n=6/group), or 200 hours (n=6/group). Immunohistochemical analysis of degraded myelin basic protein (dMBP), a marker of myelin damage, was performed. Neuroinflammation and oxidative stress were assessed by histological analysis of complement C5a, an anaphylatoxin, and 4-Hydroxynonenal (4-HNE), a marker of lipid peroxidation.dMBP integrated density was increased in the corpus callosum of DEP mice at 5 (p<0.01), 100 (p<0.01), and 200 hours (p<0.001) compared to FA mice.C5a integrated density was increased in the corpus callosum of DEP mice at 5 (p<0.01), 100 (p<0.01), and 200 hours (p<0.01) compared to FA mice. 4-HNE integrated density was increased in the corpus callosum of DEP mice at 5 (p<0.001), 100 (p=0.001), and 200 hours (p<0.001) compared to FA mice. Neuroinflammation and oxidative stress are upregulated with associated white matter injury in the corpus callosum after 5 hours of DEP exposure.Short-term DEP exposure activates inflammatory/oxidative stress pathways, which may contribute to the pathogenesis of white matter injury.Erickson et al. 2020,PMID:32182984; Chen et al. 2020,PMID:32669395.

The Effect of Antenatal Betamethasone on White Matter Inflammation and Injury in Fetal Sheep and Ventilated Preterm Lambs

2018 ◽  
Vol 40 (5-6) ◽  
pp. 497-507 ◽  
Author(s):  
Vanesa Stojanovska ◽  
Samantha K. Barton ◽  
Mary Tolcos ◽  
Andrew W. Gill ◽  
Martin Kluckow ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
White Matter ◽  
Oxygen Delivery ◽  
Late Preterm ◽  
Limited Information ◽  
Fetal Sheep ◽  
Activated Microglia ◽  
Protein Extravasation ◽  
To Receive ◽  
And Oxidative Stress

Antenatal administration of betamethasone (BM) is a common antecedent of preterm birth, but there is limited information about its impact on the acute evolution of preterm neonatal brain injury. We aimed to compare the effects of maternal BM in combination with mechanical ventilation on the white matter (WM) of late preterm sheep. At 0.85 of gestation, pregnant ewes were randomly assigned to receive intra-muscular (i.m.) saline (n = 9) or i.m. BM (n = 13). Lambs were delivered and unventilated controls (UVCSal, n = 4; UVCBM, n = 6) were humanely killed without intervention; ventilated lambs (VentSal, n = 5; VentBM, n = 7) were injuriously ventilated for 15 min, followed by conventional ventilation for 75 min. Cardiovascular and cerebral haemodynamics and oxygenation were measured continuously. The cerebral WM underwent assessment of inflammation and injury, and oxidative stress was measured in the cerebrospinal fluid (CSF). In the periventricular and subcortical WM tracts, the proportion of amoeboid (activated) microglia, the density of astrocytes, and the number of blood vessels with protein extravasation were higher in UVCBM than in UVCSal (p < 0.05 for all). During ventilation, tidal volume, mean arterial pressure, carotid blood flow, and oxygen delivery were higher in ­VentBM lambs (p < 0.05 vs. VentSal). In the subcortical WM, microglial infiltration was increased in the VentSal group compared to UVCSal. The proportion of activated microglia and protein extravasation was higher in the VentBM group compared to VentSal within the periventricular and subcortical WM tracts (p < 0.05). CSF oxidative stress was increased in the VentBM group compared to UVCSal, UVCBM, and VentSal groups (p < 0.05). Antenatal BM was associated with inflammation and vascular permeability in the WM of late preterm fetal sheep. During the immediate neonatal period, the increased carotid perfusion and oxygen delivery in BM-treated lambs was associated with increased oxidative stress, microglial activation and microvascular injury.

scholarly journals Role of Anti-oxidants in the Treatment of Vitiligo

2019 ◽  
Vol 17 (1) ◽  
pp. 49-57
Author(s):  
Amit Kumar ◽  
Sudha Agrawal ◽  
Tapan Kumar Dhali ◽  
Shankar Kumr Majhi
Keyword(s):  
Oxidative Stress ◽  
Placebo Group ◽  
Vitamin E ◽  
Primary Outcome ◽  
Antioxidant Supplementation ◽  
Significant Difference ◽  
Anti Oxidant ◽  
And Oxidative Stress

Introduction: The role of free radicals and oxidative damage in the pathophysiology of vitiligo has been documented in recent studies. Antioxidant supplementation has been reported to be useful in the treatment of vitiligo. Objective: To evaluate the role of oral antioxidants supplementation therapy in the treatment of vitiligo by assessing the onset of repigmentation and oxidative stress. Materials and Methods: A total of 80 cases of vitiligo randomized into two groups: antioxidant and placebo comprising 40 patients each and were followed up for 8 weeks for the assessment of onset of repigmentation of vitiliginous lesions as primary outcome.  The activities of Malondialdehyde (MDA), Vitamin C, and Vitamin E in serum and of Catalase (CAT) in erythrocytes of patients at baseline and at end of eight weeks were also assessed by using the spectrophotometric assay. Results: The onset of repigmentation was noted significantly earlier among the anti-oxidant group as compared to the placebo group (p=0.015). At the baseline, between the two groups, no significant difference was found in the different biochemical parameters. However, at the end of 2 months the level of MDA (p<0.001) was found to be significantly lower and that of Vitamin E (p<0.001) and CAT (p=0.005) was significantly higher among the anti-oxidants group as compared to the placebo group. Conclusion: Antioxidant supplementation carried a better response in terms of early onset of repigmentation and significant decrease in the oxidative stress, in the short follow up of two months.

Peroxiredoxin V in multiple sclerosis lesions: predominant expression by astrocytes

2007 ◽  
Vol 13 (8) ◽  
pp. 955-961 ◽  
Author(s):  
J.E. Holley ◽  
J. Newcombe ◽  
P.G. Winyard ◽  
N.J. Gutowski
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
White Matter ◽  
Human Brain ◽  
Reductase Activity ◽  
Normal Appearing White Matter ◽  
Anti Oxidant ◽  
Normal Human ◽  
Global Increase ◽  
Predominant Expression

Oxidative stress is implicated in the pathogenesis of multiple sclerosis (MS). Defence against oxidative damage is mediated by antioxidants. Peroxiredoxin V (PRDX V) is an intracellular anti-oxidant enzyme with peroxynitrite reductase activity. It is increased during inflammation, when free radical production intensifies, and is protective in an animal model of brain injury. However, little is known about PRDX V expression in the human brain. We investigated PRDX V expression in white matter from normal human brain ( n = 5) and MS patients ( n = 18), using immunohistochemistry and immunoblotting. A global increase in PRDX V was evident in MS normal-appearing white matter (NAWM) but the most striking increase was in astrocytes in MS lesions. PRDX V- positive hypertrophic reactive astrocytes were seen in acute lesions where inflammation was present. Yet surprisingly, in chronic lesions (CL), where inflammation has abated and a glial scar formed, there was strong PRDX V staining of post-reactive, scar astrocytes. Furthermore, immunoblotting analysis of tissue from two MS cases confirmed a substantial increase in PRDX V expression in CL compared with NAWM from the same individual. This might indicate ongoing oxidative stress despite the absence of histologically defined inflammation. Further investigations of this phenomenon will be of interest for therapeutic targeting. Multiple Sclerosis 2007; 13: 955—961. http://msj.sagepub.com

scholarly journals DNA Damage Responses and Oxidative Stress in Dyskeratosis Congenita.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2359-2359
Author(s):  
Larisa Pereboeva ◽  
Erik Westin ◽  
Toral Patel ◽  
Ian Flaniken ◽  
Lawrence S. Lamb ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cellular Proliferation ◽  
Dyskeratosis Congenita ◽  
Dependent Manner ◽  
Radiation Induced ◽  
Anti Oxidant ◽  
And Control ◽  
And Oxidative Stress

Abstract Abstract 2359 Introduction: Dyskeratosis congenita (DC) is an inherited multisystem disorder consisting of premature aging, cancer predisposition, bone marrow failure and the characteristic triad of mucosal leukoplakia, skin dyspigmentation and nail dystrophy. Symptomology associated with DC arises as a consequence of mutations within genes associated with telomeres and telomerase activity manifested by critically shortened telomeres in affected cells. We have previously reported a growth disadvantage and increased intracellular oxidative stress in cultured somatic cells obtained from patients with DC. We hypothesize that telomere maintenance is closely linked to dysregulation in oxidative pathways and consequent DNA damage. Our objective was to discern whether pharmacologic intervention to alleviate oxidative stress imparts a protective effect in DC cells. Methods: T lymphocytes from both DC subjects with hTERC mutations and age-matched controls were cultured and expanded in vitro using CD3/CD28 beads. DNA damage to cells was induced using paclitaxel, etoposide, or ionizing radiation during log-phase of cell growth. Cellular proliferation and apoptosis were monitored by cell counting and flow cytometry (FACS) using Annexin V antibody and propidium iodide. Western blotting was used to measure basal and radiation-induced expression of DNA damage response (DDR) proteins, including total p53 and its activated form (serine 15 phosphorylated; p53S15), p21WAF, and phosphorylated H2AX (gH2AX). Level of oxidative stress was determined by FACS using the cell-permeable fluorogenic probe DCFH and dihydroethedium (DHE) detecting reactive oxygen species (ROS). Anti-oxidants, including vitamin E and N acetyl cysteine (NAC), were used in vitro to modulate levels of oxidative stress in control and radiated cells. Results: Comparison of growth curves demonstrated a significant decrease in proliferation of T cells obtained from DC patients versus control T cells. This growth disadvantage was more pronounced following cell exposure to radiation, paclitaxel, and etoposide. To explain these differences we investigated several parameters indicative of DNA damage. DC lymphocytes had higher basal levels of apoptosis, while radiation resulted in comparable levels of apoptosis in both DC and control cultures. Similarly, DDR markers p53 and p53S15, but not p21 and g-H2AX, were basally expressed at higher levels in DC lymphocytes while radiation, in a dose-dependent manner, upregulated expression of p53, p53S15, p21 and g-H2AX in both DC and control lymphocytes. Consistent with DDR data, elevated basal levels of ROS were found in short term DC cultures. Additionally, in a dose dependent manner, the anti-oxidant NAC partially ameliorated the growth disadvantage of DC cells. Importantly, NAC also decreased radiation-induced apoptosis and oxidative stress in DC cells. Studies are ongoing to characterize the modulation of DDR markers in NAC-treated cells. Conclusions: DC is an important disease model for studying the effects of telomere shortening on cellular proliferation and other molecular pathways involved in cell senescence and aging. Our findings of elevated basal levels of apoptosis, DDR proteins and oxidative stress in DC lymphocytes, as well as increased sensitivity of DC cells to cytotoxic agents suggests a role of telomerase and/or telomere length in regulating oxidative and DNA damage response pathways. This data also validates the clinical finding of DC patients' intolerance to myeloablative therapy. Finally a pharmacologic approach to reduce oxidative stress may alleviate some of the untoward toxicities associated with current cytotoxic treatments in DC. Clinical trials testing various anti-oxidant therapies are currently under design. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Lactobacillus casei Strain Shirota Enhances the Ability of Geniposide to Activate SIRT1 and Decrease Inflammation and Oxidative Stress in Septic Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Chao Mai ◽  
Li Qiu ◽  
Yong Zeng ◽  
Xingqin Tan
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
Lactobacillus Casei ◽  
P53 Protein ◽  
Cecal Ligation ◽  
Morris Water Maze Test ◽  
Gardenia Jasminoides ◽  
Tnf Α ◽  
Anti Oxidant ◽  
And Oxidative Stress

Gardenia jasminoides Ellis is rich in geniposide, which can be transformed into the anti-oxidant and anti-inflammatory agent genipin. Genipin exhibits greater efficacy than geniposide, but it is unstable and difficult to preserve. In this study, a mouse model for sepsis was established by cecal ligation and puncture, and then we explored the effects and mechanism of Lactobacillus casei strain Shirota (LcS) on the enhancement of the ability of geniposide to reduce sepsis and decrease inflammatory and oxidative levels in mice by the regulation of sirtuin type 1 (SIRT1). The mice were evaluated and analyzed by the open field test, Morris water maze test, flow cytometry, kit assay, qPCR, and western blot. The LcS + geniposide increased the survival rate in mice with sepsis, and increased the total travel distance, number of times the mice stood up, amount of time the mice spent grooming their fur, duration in the target quadrant, and crossing area number. The testing of mouse nerve cells showed that LcS + geniposide reduced the rate of nerve cell apoptosis caused by sepsis. LcS + geniposide also decreased the amount of inflammatory-related indicators of TNF-α, IL-6, and IL-1β, and the oxidation-related levels of malondialdehyde (MDA) in the hippocampi of septic mice, and it increased the oxidase activities of superoxide dismutase (SOD) and catalase (CAT). Additionally, LcS + geniposide increased the SOD1, SOD2, and CAT mRNA expression in the hippocampi of mice with sepsis and decreased the expression of TNF-α, IL-1β, NF-κB, and p53 mRNA. LcS+geniposide also increased the SIRT1 protein expression and decreased the Ac-FOXO1, Ac-NF-κB, and Ac-p53 protein expression in the hippocampi of mice with sepsis. We also observed that LcS + geniposide decreased the inflammatory and oxidative damage in the mice with sepsis. The effect of LcS + geniposide was similar to that of the drug dexamethasone and stronger than the effect of geniposide utilized alone. LcS also enhanced the ability of geniposide to activate SIRT1 and decrease the inflammation and oxidative stress in the septic mice, and it achieved an effect same with that obtained by the use of the drug dexamethasone.

Abstract WP112: Residual Damage is Reduced Following Human Umbilical Tissue Derived Cell Infusion in a Non-human Primate Model of Cortical Injury

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Mary E Orczykowski ◽  
Eli Shobin ◽  
Samantha M Calderazzo ◽  
Brian C Kramer ◽  
Farzad Mortazavi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
White Matter ◽  
Motor Cortex ◽  
Oxidative Damage ◽  
Primary Motor Cortex ◽  
Primate Model ◽  
Cortical Injury ◽  
Activated Microglia ◽  
And Oxidative Stress ◽  
Human Primate

Introduction: Stroke is the leading cause of long-term disability in the United States due to impairments that endure after brain injury. While studies in rodent models have evaluated numerous neurorestorative treatments following stroke, none have received FDA approval. We evaluated a therapy using human umbilical tissue-derived cells (hUTC) as a potential neurorestorative treatment in our non-human primate model of cortical injury limited to the hand area of primary motor cortex. Given treatment 24 hours after injury, hUTC treated monkeys showed a significantly greater degree of recovery of fine motor function compared to vehicle treated controls (Moore et al., 2013). To explore the effect of hUTC, histopathological markers of inflammation and oxidative stress were assessed. Hypothesis: Treatment with hUTC will enhance the recruitment of glia to the injury and reduce the cascade of inflammation and oxidative stress. Methods: Using immunohistochemistry, activated microglia (LN3), reactive astrocytes (GFAP), oxidative damage (4HNE), and accumulated hemosiderin (Perls’ Prussian Blue) were quantified in ipsilesional primary motor cortex and underlying white matter. Microglia were counted using unbiased stereology. A Sholl Analysis was performed on traced perilesional astrocytes. The area of oxidative damage and hemosiderin was assessed using densitometry. Results: Compared to vehicle controls, density of activated microglia in the hUTC treated group approached a significant increase in the perilesional gray and white matter (p=0.070; p=0.092). Astrocytes exhibited more complex processes in treated monkeys (p=0.042). Staining for 4HNE was significantly reduced in white matter underlying the lesion in treated monkeys (p=0.033). Lastly, both the area and intensity of Perls’ staining for hemosiderin was significantly reduced in the perilesional area of treated monkeys (p=0.045; p=0.001). Conclusions: Treatment with hUTC resulted in increased activation of microglia and complexity of reactive astrocyte processes as well as reduced post-lesion oxidative damage and hemosiderin deposition. This suggests the hUTC treatment enhanced recovery, in part, by recruitment of glial cells that limited the damage following cortical injury.

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